The present invention, in some embodiments thereof, relates to antibodies which can specifically bind complexes of MHC and an MHC-restricted HIV antigenic peptide and uses thereof in the diagnosis and treatment of HIV/AIDS in a subject.
Acquired immune deficiency syndrome (AIDS), a disease that severely compromises the human immune system, is caused by the human immunodeficiency virus (HIV). Global statistics indicated that in 1998 as many as 33 million people worldwide were infected with the virus.
HIV testing, and especially early diagnosis of infection, is integral to HIV prevention, treatment and care efforts. Screening provides an opportunity for people to receive counseling and information about risk reduction. Early knowledge of HIV status, particularly for those who are serologically HIV positive, can link them to medical care and services that can reduce morbidity and mortality and improve their quality of life.
Detection of HIV antibodies in the blood continues to be the gold standard. However, due to the lag phase, which elapses between HIV exposure and initiation of HIV antibody response, early diagnosis of HIV infection is currently limited.
Therapeutic intervention for control of HIV infection include competitive inhibitors of apartyl protease such as, saquinavir, indinavir, ritonavir, nelfinavir and amprenavir; inhibitors of reverse transcriptase such as zidovudine, didanosine, stavudine, lamivudine, zalcitabine and abacavir; and non-nucleoside reverse transcriptase inhibitors, nevaripine, delavaridine and efavirenz, which inhibit the synthesis of viral cDNA via a non-competitive mechanism. However, although such drugs have been separately employed to reduce viral replication, the HIV virus rapidly evolves and develops resistance thereagainst.
Peptides derived from cytosolic-proteins which are mainly endogenously synthesized proteins are bound to class I major histocompatibility complex (MHC) molecules that are expressed on the surface of nearly all cells and are recognized by CD8+ cytotoxic T lymphocytes (CTLs)
The immune system is capable of mounting potent attacks on invading viruses and eliminating many of them. Those that persist have often evolved strategies to interfere with the pathway that presents viral peptide antigens bound to class I MHC molecules so that they can evade attack by CTL. Significance progress has been achieved, in recent years, in the understanding of cellular immune response against viral infected-cells and tumor cells. This is mainly due to the use of polyvalent, soluble peptide-HLA complexes that specifically bind the T-cell receptor (TCR), and enable the identification and characterization of antigen-specific T lymphocytes.
PCT Publication No. WO 03/068201 discloses antibodies having a T-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease.
U.S. patent application Ser. Nos. 10/371,942 and 11/582,416 disclose MHC-peptide complex binding ligands.
PCT Publication No. WO 04/084798 discloses antigen-presenting complex-binding compositions and uses thereof.